Uninhibited proteolysis of lung elastic tissue may play a role in the pathogenesis of emphysema. The in vivo enzymes which might play a role in man are unknown but the human alveolar macrophages contain a high level of an elastase-like esterase. In order to evaluate the hypothesis that proteolysis can lead to emphysema in man a necessity would be to isolate, purify, and characterize responsible enzymes. Large numbers of viable macrophage can be obtained by lavaging surgically resected lungs. We propose to purify human alveolar macrophage elastase by affinity chromatography or immunologic techniques and study its mechanisms of catalysis and mechanisms of inhibition. The ability of the enzyme to induce remodeling of animal lung will be studied. We also propose to evaluate compounds which might be used chemotherapeutically to inhibit this elastase by measuring inhibition of the enzyme in vitro and in vivo.